The pathological diagnosis report of hepatocellular carcinoma generally consists of a description of the gross specimen, microscopic description, immunohistochemical findings, and molecular pathology findings.
Major specimen description
The gross specimen description is the visualization of the submitted tissue, including the size of the submitted liver tissue, the number of tumors visible on the cut surface, the size, color, and texture of the tumors, whether they are clearly defined from the surrounding normal tissue, and the color and texture of the surrounding normal liver tissue.
Microscopic description
The microscopic description is first divided into primary liver cancer and metastatic liver cancer. The different origins determine different treatments and prognosis.
- Primary hepatocellular carcinoma collectively refers to malignant tumors originating from hepatocytes and intrahepatic bile duct epithelial cells, with hepatocellular carcinoma and intrahepatic bile duct carcinoma being the most common.
- Metastatic liver cancer refers to a history of malignant tumors elsewhere in the body, most commonly from the stomach and intestines to the liver.
Microscopic morphology is an important feature that distinguishes pathology from clinical and imaging, mainly including histological staging, grading, and growth pattern of the tumor.
Histologic staging
Histologic types of hepatocellular carcinoma commonly include fine-beam, coarse-beam, pseudoglandular ductal, and masseter types, and special types include clear cell, lipid-rich, spindle cell, and undifferentiated types.
Grading
The degree of differentiation of hepatocellular carcinoma is graded by the internationally used Edmondson-Steiner four-grade scale, from mild to severe, as grade I (highly differentiated), grade II (moderately differentiated), grade III (poorly differentiated), and grade IV (undifferentiated).
Intrahepatic cholangiocarcinoma is most commonly adenocarcinoma, but can also present with a variety of histologically and cytologically specific types, including adenosquamous and squamous carcinoma, mucinous carcinoma, indolent cell carcinoma, clear cell carcinoma, mucinous epidermodysplasia-like carcinoma, lymphoepithelioma-like carcinoma and sarcomatoid carcinoma. The degree of differentiation is graded from mild to severe as grade I (highly differentiated), grade II (moderately differentiated), and grade III (poorly differentiated).
Mode of growth
Tumor growth pattern, including peri-cancerous infiltration, envelope invasion or breakthrough, microvascular invasion, and satellite nodules, is an important predictor of postoperative recurrence risk.
Microvascular invasion (MVI), also known as microvascular thrombosis, is a nesting mass of cancer cells (>50 cancer cells) seen microscopically within the lumen of endothelium-lined vessels, including:
- M0: no MVI detected;
- M1 (low-risk group): no greater than 5 MVI and occurring in the proximal hepatic tissue area (no greater than 1 cm);
- M2 (high-risk group): greater than 5 MVIs, or MVIs occurring in the distal paracancerous liver tissue area (greater than 1 cm).
If only a small number of loosely suspended cancer cells (less than 50) are present in the vasculature, this is considered a low risk of recurrence.
Satellite nodules (subfoci) are primarily small cancer foci separated from the main tumor and are predictors of poor overall survival.
Immunohistochemistry
Immunohistochemical tests are mainly used to differentiate benign and malignant hepatocellular tumors, hepatocellular carcinoma from intrahepatic cholangiocarcinoma and other specific types of tumors of the liver, and primary liver cancer from metastatic liver cancer.
Common markers for hepatocellular carcinoma include HepPar-1, GPC-3, CD34, pCEA, CD10, arginase-1, HSP70, GS, AFP, and others. Common markers for intrahepatic cholangiocarcinoma are CK19, CK7, MUC-1, etc.
Biphenotypic hepatocellular carcinoma is a specific subtype of hepatocellular carcinoma that presents as a morphologically typical hepatocellular carcinoma that significantly expresses markers of both hepatocellular carcinoma and cholangiocarcinoma, which is more malignant and has a worse prognosis because of its dual phenotypic features and can only be diagnosed by immunohistochemistry.
Molecular pathology
Molecular pathology remains the current direction and trend of research development, and its practical implications for the clinic are still under investigation and development.
Other frequently asked questions about pathology reports
The following questions are also frequently asked by patients about pathology reports for liver cancer.
What does “with necrosis” mean in the pathology report?
What does “necrosis” mean in the pathology report?
Necrosis is a more common concomitant form of tumor, probably due to rapid growth of tumor tissue and lack of central blood supply to the tumor, and is an aggressive manifestation of the tumor.
The effect of preoperative treatment is also reflected by extensive necrosis of tumor tissue if preoperative treatment has been done.
What does “with lipoatrophy” mean in the pathology report?
What does “with steatosis” mean in the pathology report?
Steatosis of the peripheral liver tissue is mainly caused by impaired lipoprotein synthesis, which in severe cases is commonly referred to as fatty liver, and is a reversible injury that can return to normal after the cause is eliminated.
Tumor tissue can also develop steatosis, i.e., lipid-rich hepatocellular carcinoma, with better polysynthesis.
What does “large and small cell changes” mean in the pathology report?
What does “large and small cell changes” mean in the pathology report?
Large cell metaplasia is an enlarged nucleus and cells of hepatocytes with a constant nucleoplasmic ratio. The presence of macrocytosis in the liver with hepatitis B or C cirrhosis is an independent risk factor for the subsequent development of hepatocellular carcinoma. At the very least, macrocytosis suggests the occurrence of chronic injury that predisposes to hepatocarcinogenesis.
Small cell metaplasia refers to a decrease in hepatocyte size, an increase in the nucleoplasmic ratio, and a crowded nucleus appearance. It is now considered to be a definite precancerous lesion.